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L Fan

Publications and source records attributed to L Fan.

At least 19 recordsLinked to original sources
PubMed2006

Developing master keys to brain pathology, cancer and aging from the structural biology of proteins controlling reactive oxygen species and DNA repair.

This review is focused on proteins with key roles in pathways controlling either reactive oxygen species or DNA damage responses, both of which are essential for preserving the nervous system. An imbalance of reactive oxygen species or inappropriate DNA damage response likely causes mutational or cytotoxic outcomes, which may lead to cancer and/or aging phenotypes. Moreover, individuals with hereditary disorders in proteins of these cellular pathways have significant neurological abnormalities. Mutations in a superoxide dismutase, which removes oxygen free radicals, may cause the neurodegenerative disease amyotrophic lateral sclerosis. Additionally, DNA repair disorders that affect the brain to various extents include ataxia-telangiectasia-like disorder, Cockayne syndrome or Werner syndrome. Here, we highlight recent advances gained through structural biochemistry studies on enzymes linked to these disorders and other related enzymes acting within the same cellular pathways. We describe the current understanding of how these vital proteins coordinate chemical steps and integrate cellular signaling and response events. Significantly, these structural studies may provide a set of master keys to developing a unified understanding of the survival mechanisms utilized after insults by reactive oxygen species and genotoxic agents, and also provide a basis for developing an informed intervention in brain tumor and neurodegenerative disease progression.

Aging↗
PubMed2006

Incongruent evolution of chromosomal size in rice.

To investigate genome size evolution, it is usually informative to compare closely related species that vary dramatically in genome size. A whole genome duplication (polyploidy) that occurred in rice (Oryza sativa) about 70 million years ago has been well documented based on current genome sequencing. The presence of three distinct duplicate blocks from the polyploidy, of which one duplicated segment in a block is intact (no sequencing gap) and less than half the length of its syntenic duplicate segment, provided an excellent opportunity for elucidating the causes of their size variation during the post-polyploid time. The results indicated that incongruent patterns (shrunken, balanced and inflated) of chromosomal size evolution occurred in the three duplicate blocks, spanning over 30 Mb among chromosomes 2, 3, 6, 7, and 10, with an average of 20.3% for each. DNA sequences of chromosomes 2 and 3 appeared to had become as short as about half of their initial sequence lengths, chromosomes 6 and 7 had remained basically balanced, and chromosome 10 had become dramatically enlarged (approximately 70%). The size difference between duplicate segments of rice was mainly caused by variations in non-repetitive DNA loss. Amplification of long terminal repeat retrotransposons also played an important role. Moreover, a relationship seems to exist between the chromosomal size differences and the nonhomologous combination in corresponding regions in the rice genome. These findings help shed light on the evolutionary mechanism of genomic sequence variation after polyploidy and genome size evolution.

Base Sequence↗
PubMed2005

Treatment of short gut syndrome with early living related small bowel transplantation.

AIM: To investigate the results of treating short bowel syndrome with an early living related small bowel transplantation (SBT). METHODS: A 17-year-old boy with a 20-cm-long residual intestine due to necrotic volvulus received an early living related SBT from his mother. Donor-specific blood transfusion was performed for 8 weeks before transplantation, each time for 50 mL every week. Cytomegalovirus status in both donor and recipient was negative. A 160-cm distal ileal segment was removed from the donor. The graft ilecolic artery and vein were anastomosed to the recipient's infrarenal aorta and caval vein. The proximal end of the graft was anastomosed end-to-end to the residual recipient jejunum; the distal anastomosis, between the distal end of the graft and transverse colon. An ileostomy was also performed. Immunosuppression, infection prophylaxis, and antithrombotic and nutrition support were given postoperatively. RESULTS: The donor had an uneventful recovery. No technical complications were observed. The recipient was alive and well at 31 weeks after the operation. No graft rejection or infection was observed. He was off TPN 8 weeks after the operation and took low-fat food. The D-xylose test in the recipient was almost normal. CONCLUSIONS: Early living related small intestine transplantation is a good treatment for short bowel syndrome.

Adolescent↗
PubMed2005

Adsorption of aflatoxin B1 on montmorillonite.

The isothermal adsorption and the adsorptive mechanism of aflatoxin B1 (AFB1) on calcium montmorillonite (Mont) were studied in vitro trials. The maximum amounts of AFB1 on Mont in aqueous solution at 2 and pH 8 were 613.5 and 628.9 microg of AFB1 /g of Mont, respectively. The structure of AFB1-Mont was measured by x-ray diffraction and infrared absorption spectrum. The results suggested that the mechanism of AFB1 on Mont was AFB1 sorbed onto the edge of Mont by a double hydrogen bond, and AFB1 molecules did not penetrate into the interlayer area of Mont. The Mont, when added to the diet of broiler chicken at 0.5%, significantly diminished the adverse effects of feeding 200 microg of AFB1 /kg of feed. And the concentrations of Ca, P, Cu, Fe, Zn in the broiler bones were not affected by AFB1 and Mont, but the concentrations of Mn, Pb, and F were decreased by Mont.

Adsorption↗
PubMed2005

Tissue factor enhances protease-activated receptor-2-mediated factor VIIa cell proliferative properties.

In addition to its hemostatic functions, factor (F)VIIa exhibits cell proliferative properties as seen in angiogenesis and tumor growth. A role for tissue factor (TF) and protease-activated receptors (PAR)-1 and -2 in cell proliferation remain to be clarified. We tested the hypothesis that FVIIa induces cell proliferation by a mechanism involving TF and PAR-2. Human recombinant FVIIa induced cell proliferation of human BOSC23 cells transfected with plasmid containing human TF DNA sequence. Because DNA primase 1 (PRIM1) plays an essential role in cell proliferation, we used the cloned PRIM1 promoter upstream of the reporter gene chloramphenicol acetyl transferase (CAT) to elucidate the mode of action of FVIIa. FVIIa evoked a dose-dependent increase in cell proliferation and PRIM1 induction, which were markedly potentiated (4-5-fold) by the presence of TF and abrogated by TF antisense oligonucleotide. PRIM1 induction by FVIIa was also abolished by PAR-2 but not by PAR-1 antisense. In contrast, thrombin induced a small increase in CAT activity which was unaffected by TF, but was prevented only by PAR-1 antisense as well as the thrombin inhibitor hirudin. Proliferative properties of FVIIa were associated with a TF-dependent increase in intracellular calcium and were mediated by a concordant phosphorylation of p44/42 MAP kinase. In conclusion, data reveal that FVIIa induces PRIM1 and ensuing cellular proliferation via a TF- and of the PARs entirely PAR-2-dependent pathway, in distinction to that of thrombin which is PAR-1-dependent and TF-independent. We speculate that FVIIa-TF-PAR-2 inhibitors may be effective in suppressing cell proliferation.

Blotting, Northern↗
PubMed2005

Evaluation of the profile of thrombin generation during the process of whole blood clotting as assessed by thrombelastography.

The objective of this study was to evaluate the possibility of linking the tracing of whole blood clotting in a thrombelastograph (TEG) hemostasis system with the generation of thrombin assessed by thrombin/antithrombin complex (TAT). Citrated whole blood containing corn trypsin inhibitor from volunteers was clotted in the presence of CaCl2 and tissue factor. Clotting was monitored with the eight channels of a TEG system. At different time points, the whole blood TEG reaction cups were kept in a cold quenching solution, centrifuged, and the supernatants were kept at -80 degrees C until assayed for TAT by ELISA. The total thrombus generation (TTG) was calculated from the first derivative of the TEG waveform and was compared with thrombin generation measured by TAT. The two vector values--the TAT thrombin generation data and the corresponding TEG TTG--were analyzed using Pearson correlation coefficients (r) and linear, non-linear and natural log (ln) transformation of TAT values for least-squares goodness-of-fit curves. The best least-squares fit is an exponential curve. Linearizing using the ln of the TAT thrombin generation variable produces the same r (0.94) as of the exponential curve. The prediction equation is y = 8.0465 + 0.0005x (P < or = 0.0001), where y is the TAT thrombin generation variable in the ln transformation and x is the TEG TTG variable. The high magnitude of r and the high significance of the prediction equation demonstrate the high efficacy of the prediction of TAT thrombin generation by the use of TEG TTG.

Antithrombin III↗
PubMed2004

Sensitive high-performance liquid chromatography/mass spectrometry method for determination of steviol in rat plasma.

The main toxicological concern of stevioside, a highly potent sweetener from S. rebaudiana, is its main metabolite, steviol. To determine very low levels of steviol in in vivo experiments, a sensitive liquid chromatography/atmospheric pressure chemical ionization mass spectrometry (LC/APCI-MS) method was developed for quantifying steviol in rat plasma after oral administration of a single dose of stevioside (0.5 g/kg). The sample preparation uses liquid-liquid extraction with tert-butyl methyl ether in an acidic environment. The retention time of steviol was 10.5 min. The assay was linear over the range 2-1000 ng/mL with a lower limit of detection of 1 ng/mL. The intra- and inter-day precision were <5 and <7%, respectively, and the accuracy was in the range 95-108%. The steviol concentration profile in rat plasma was determined.

Administration, Oral↗
PubMed2004

Real-time identification and archiving of micro-embolic Doppler signals using a knowledge-based DSP system.

Identification of micro-emboli in the cerebral circulation using transcranial Doppler ultrasound provides valuable clinical information, but, currently, embolic signal detection and analysis are significantly limited because they mainly rely on costly off-line analysis by human experts. In this study, a reliable, high-resolution, real-time automated system for the detection and archiving of embolic signals was designed and implemented using expert system theory and modern DSP technology. Preliminary tests were conducted to evaluate the functions and the performance of the system using data from ten carotid endarterectomy patients and two normal volunteers. Using the widely accepted 7 dB threshold for human reliability and a human expert, majority-decision gold standard, the real-time system reached sensitivity and specificity of 93.6% and 99.3%, respectively, which were close to the results obtained by three human experts under ideal laboratory conditions (90.1% and 99.8%, 98.4% and 99.9%, 98.9 and 99.9%). The new system has the potential to be used either as a bedside monitoring and signal acquisition device, or as a laboratory investigation tool.

Endarterectomy, Carotid↗
PubMed2004

Association between dynamic cerebral autoregulation and mortality in severe head injury.

The objective of the study was to test the hypothesis that dynamic cerebral pressure-autoregulation is associated with the outcome of patients with severe head injury and to derive optimal criteria for future studies on the predictive value of autoregulation indices. Repeated measurements were performed on 32 patients with severe head injury. Arterial blood pressure (ABP) was measured continuously with an intravascular catheter, intracranial pressure (ICP) was recorded with a subdural semiconductor transducer and cerebral blood flow velocity (CBFV) was measured with Doppler ultrasound in the middle cerebral artery. Transfer function analysis was performed on mean beat-to-beat values, using ABP or CBFV as input variables and CBFV or ICP as the output variables. A dynamic index of autoregulation (ARI) ranging between 0 and 9 was extracted from the CBFV step response for a change in ABP. No significant differences between survivors and non-survivors were found due to mean values of ICP, ABP, CPP, CBFV, pCO2, GCS, age or heart rate. The transfer functions between ABP-ICP and CBFV-ICP did not show any significant differences either. The median [lower, upper quartiles] ARI was significantly lower for non-survivors compared with survivors [4.8 (0.0, 5.9) v. 6.9 (5.9, 7.4), p= 0.004]. The correlation between ARI and GOS was also significant (r=0.464, p=0.011). Cohen's coefficient was optimal for a threshold of ARI= 5.86 (kappa 0.51, p=0.0036), leading to a sensitivity for death of 75%, specificity=76.5%, odds ratio =9.75 and overall precision = 75.8%. The difference in ARI values between survivors and non-survivors persisted when results were adjusted for GCS (p = 0.028). A similar analysis for the Marshall CT scale did not reach significance (p = 0.072). A logistic regression analysis confirmed that apart from the ARI, no other variables had a significant contribution to predict outcome. In this group of patients, death following severe head injury could not be explained by traditional indices of risk, but was strongly correlated to indices of dynamic cerebral pressure-autoregulation extracted by means of transfer function analysis. Future studies using a prospective design are needed to validate the predictive value of the ARI index, as estimated by transfer function analysis, in relation to death and other unfavourable outcomes.

Adolescent↗
PubMed2004

The genetic epidemiology of alopecia areata in China.

BACKGROUND: Alopecia areata (AA) is hypothesized to be an organ-specific autoimmune disease with genetic predisposition and an environmental trigger. There are few clinical data in Asians. OBJECTIVES: To describe the genetic epidemiological features of AA patients in China and to determine the possible genetic model for AA. METHODS: Data for 1032 patients with AA were obtained by questionnaire in the Institute of Dermatology of Anhui Medical University in China from 2001 to 2003. Complex segregation analysis and heritability analysis were performed using Falconer's method, EPI INFO 6.0 and SAGE-REGTL programs. RESULTS: In total, 1032 AA patients (male/female ratio 1.1 : 1) were enrolled, representing 0.94% of the total number of cases seen in our outpatient clinic during that time. The mean +/- SD age of onset was 28.98 +/- 13.43 years. The difference between the mean age of onset in males and females was not significant. Most patients (82.6%) experienced their first episode of AA within the first four decades of life. A positive family history of AA was obtained in 87 patients (8.4%). The prevalence of AA in first-, second- and third-degree relatives of the proband with AA was 1.6%, 0.19% and 0.03%, respectively. These figures were higher than those in controls. A greater severity and longer duration of AA were seen in the early onset group than in the late-onset group. The early onset group also had more affected first- and second-degree relatives. The heritability of AA in first-, second- and third-degree relatives was 47.16%, 42.53% and 22.29%, respectively. Based on the REGTL results, the best model was a polygenic additive model for AA. CONCLUSIONS: The effect of genetic factors is strong in AA, but environmental factors such as infection and psychological stress may still play an important role. Our findings on the genetics of AA are consistent with a polygenic additive mode of inheritance.

Adolescent↗
PubMed2003

L523S, an RNA-binding protein as a potential therapeutic target for lung cancer.

Approaches to vaccine-based immunotherapy of human cancer may ultimately require targets that are both tumour-specific and immunogenic. In order to generate specific antitumour immune responses to lung cancer, we have sought lung cancer-specific proteins that can be targeted for adjuvant vaccine therapy. By using a combination of cDNA subtraction and microarray analysis, we previously reported the identification of an RNA-binding protein within the KOC family, L523S, to be overexpressed in squamous cell cancers of the lung. We show here that L523S exhibits significant potential for vaccine immunotherapy of lung cancer. As an oncofetal protein, L523S is normally expressed in early embryonic tissues, yet it is re-expressed in a high percentage of nonsmall cell lung carcinoma. The specificity of L523S expression in lung cancer was demonstrated by both mRNA and protein measurements using real-time PCR, Western blot, and immunohistochemistry analyses. Furthermore, we show that immunological tolerance of L523S is naturally broken in lung cancer patients, as evidenced by detectable antibody responses to recombinant L523S protein in eight of 17 lung pleural effusions from lung cancer patients. Collectively, our studies suggest that L523S may be an important marker of malignant progression in human lung cancer, and further suggest that treatment approaches based on L523S as an immunogenic target are worthy of pursuit.

Biomarkers, Tumor↗
PubMed2002

A novel conditional Akt 'survival switch' reversibly protects cells from apoptosis.

The anti-apoptotic Akt kinase is commonly activated by survival factors following plasma membrane relocalization attributable to the interaction of its pleckstrin homology (PH) domain with phosphatidylinositol 3-kinase (PI3K)-generated PI3,4-P(2) and PI3,4,5-P(3). Once activated, Akt can prevent or delay apoptosis by phosphorylation-dependent inhibition or activation of multiple signaling molecules involved in apoptosis, such as BAD, caspase-9, GSK3, and NF-kappaB and forkhead family transcription factors. Here, we describe and characterize a novel, conditional Akt controlled by chemically induced dimerization (CID). In this approach, the Akt PH domain has been replaced with the rapamycin (and FK506)-binding domain, FKBP12, to make F3-DeltaPH.Akt. To effect membrane recruitment, a myristoylated rapamycin-binding domain from FRAP/mTOR, called M-FRB, binds to lipid permeable rapamycin (and non-bioactive synthetic 'rapalogs'), leading to reversible heterodimerization of M-FRB with FKBP-DeltaPH.Akt. Like endogenous c-Akt, we show that the kinase activity of membrane-localized F3-DeltaPH.Akt correlates strongly with phosphorylation at T308 and S473; however, unlike c-Akt, phosphorylation and activation of inducible Akt (iAkt) is largely PI3K independent. CID-mediated activation of iAkt results in phosphorylation of GSK3, and contributes to NF-kappaB activation in vivo in a dose-sensitive manner. Finally, in Jurkat T cells stably expressing iAkt, CID-induced Akt activation rescued cells from apoptosis triggered by multiple apoptotic stimuli, including staurosporine, anti-Fas antibodies, PI3K inhibitors and the DNA damaging agent, etoposide. This novel inducible Akt should be useful for identifying new Akt substrates and for reversibly protecting tissue from apoptosis due to ischemic injury or immunological attack.

Apoptosis↗
PubMed2002

Interaction of ozone and negative air ions to control micro-organisms.

AIMS: The aims of this study were to investigate the effect of ozone and/or negative air ions (NAI) on the viability of bacteria. METHODS AND RESULTS: Dilute cell suspensions of Pseudomonas fluorescens, Erwinia carotovora pv. carotovora and Escherichia coli were inoculated onto agar and subsequently exposed to ozone and/or NAI. Ozone concentration was maintained at 100 +/- 5 nl l-1 and NAI at 106 ml-1. When exposed to a combination of ozone and NAI, viability among all three bacterial species decreased more rapidly when they were inoculated onto potato dextrose agar (PDA) than onto nutrient agar (NA). A subsequent test examined the effect of ozone and NAI alone or in combination on the bacteria inoculated onto PDA only. Treatment with NAI alone had no killing effect on any of the bacterial species. However, a strong interaction between ozone and NAI was observed. Pseudomonas fluorescens was most susceptible to the combined treatment. Cell viability was reduced to 0.7% after 6 h, while 76% of the cells remained viable when exposed to ozone alone. Viability of Erwinia carotovora pv. carotovora was reduced to 4% after 6 h in the combined treatment compared with 69% when exposed to ozone alone. Escherichia coli was relatively more resistant to the combined treatment; viability was reduced to 40% after 11 h compared with 70% in the ozone alone treatment. CONCLUSIONS: A strong synergism between ozone and NAI on bacterial cell death was found, but the degree of this effect varied depending on bacterial species. SIGNIFICANCE AND IMPACT OF THE STUDY: The synergism of ozone with NAI may provide an effective method of reducing food-borne disease and decay of fresh produce.

Air Microbiology↗
PubMed2002

Assessment of dynamic cerebral autoregulation based on spontaneous fluctuations in arterial blood pressure and intracranial pressure.

Assessments of dynamic cerebral autoregulation usually measure the cerebral blood flow velocity (CBFV) response to changes in arterial blood pressure (ABP). We studied the effect of substituting ABP by cerebral perfusion pressure (CPP), expressed as the difference between ABP and intracranial pressure (ICP), in estimates of dynamic autoregulation obtained by transfer function analysis. CBFV, ABP and ICP were recorded during periods of physiological stability in 30 patients with severe head injury. Transfer function analysis was performed using the following combinations of input-output variables: ABP-CBFV, CPP-CBFV and CBFV-ICP. Frequency and time-domain (step response) functions were averaged for recordings with mean ICP < 20 mmHg (group A) and mean ICP > or = 20 mmHg (group B). The ABP-CBFV transfer function parameters and step response for group A were similar to previous studies in normal subjects, but group B showed deterioration of dynamic autoregulation. Radically different step responses were obtained from both groups for the CPP-CBFV transfer function and the coherence was not significantly improved. The CBFV-ICP transfer function had the highest values of coherence and indicates that changes in CBFV are the cause of spontaneous fluctuations in ICP. Furthermore, the ICP step response plateau was significantly higher for group B than for group A. An alternative calculation of the CBFV step response to changes in CPP resembled the corresponding responses for the ABP input. For spontaneous fluctuations in ABP, ICP and CBFV, it is not possible to calculate the CPP-CBFV transfer function directly due to the high positive correlation between ICP and CBFV, but an alternative estimate can be obtained by using the CBFV-ICP transfer function. The latter could also be useful as a method to assess intracranial compliance in head injury patients.

Adult↗
PubMed2001

L552S, an alternatively spliced isoform of XAGE-1, is over-expressed in lung adenocarcinoma.

Using a combination of cDNA subtraction and microarray analysis, we report here the identification and characterization of L552S, an over-expressed, alternatively spliced isoform of XAGE-1 in lung adenocarcinoma. Real-time RT-PCR analysis shows that L552S is expressed at levels greater than 10-fold in 12 of 25 lung adenocarcinoma tumors compared with the highest expression level found in all normal tissues tested. L552S is expressed in both early and late stages of lung adenocarcinoma, but it was not detected in large cell carcinoma, small cell carcinoma, or atypical lung neuroendocrine carcinoid. The full-length cDNA for L552S comprises 770 bp and encodes a polypeptide of 160 amino acids. C-terminal 94 amino acids of L552S are identical to a cancer testis antigen, XAGE-1, found in Ewing's sarcoma. Genomic sequence analysis has revealed that L552S and XAGE-1 are alternatively spliced isoforms, and expression of both L552S and XAGE-1 isoforms are present in lung adenocarcinoma. Immunohistochemistry analysis using affinity purified L552S polyclonal antibodies demonstrated specific nuclear staining in 10 of 12 lung adenocarcinoma samples. Furthermore, antibody responses to recombinant L552S protein were observed in seven of 17 lung pleural effusion fluids of lung cancer patients. These results strongly imply that L552S protein is immunogenic and suggest that it might have use as a vaccine target for lung cancer.

Adenocarcinoma↗